P401: INNOVATIVE REDUCED-DOSE CHEMOTHERAPY FOLLOWED BY BLINATUMOMAB INDUCTION THERAPY FOR SUCCESSFUL MANAGEMENT OF TREATMENT NAIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA ADULTS: A MULTICENTER, REAL-WORLD STUDY
Authors: Jing Lu, Huifen Zhou, Xin Zhou, Yonggong Yang, Laigen Tong, Miao Miao, Xiaofei Yang, Suning Chen
Journal: HemaSphere (2023)

Background: B-cell precursor acute lymphoblastic leukemia (B-ALL) is a hematological malignancy characterized by proliferation and accumulation of B-cell lymphoid progenitor cells in the bone marrow or in extramedullary sites. Since half of the adult patients with B-ALL relapse leading to poor survival outcomes, the treatment of adult B-ALL still remains a major challenge. However, newer targeted and immuno-therapies have improved the treatment of relapsed/refractory B-ALL patients. Blinatumomab, a bispecific anti-CD3 and anti-CD19 monoclonal antibody, has shown significant improvement in clinical outcomes with higher molecular response and longer survival in patients with relapsed/refractory as well as minimal residual disease (MRD)-positive B-ALL and is approved for use in such patients. Encouraging clinical efficacy data have also been observed for blinatumomab in the early line setting as sequential therapy in B-ALL. However, the efficacy of single agent blinatumomab does not meet the needs of young adult treatment, and the combination of treatment with chemotherapy tends to combine with higher levels of chemotherapy toxicity. Also, there is a gap between real-world results and clinical trials. Aims: To evaluate the efficacy and safety of blinatumomab as induction therapy in newly diagnosed patients with B-ALL receiving reduced-dose chemotherapy in real-world. And to explore the optimal balance of combining chemotherapy and immunotherapy. Methods: This is a multicenter, retrospective, observational real-world cohort analysis which included newly diagnosed patients with B-ALL at four hematology treatment centers between December 2021 and October 2022 in China. All patients received reduced-dose chemotherapy (RDC, including idarubicin, vindesine, and dexamethasone) for 1-3 weeks followed by blinatumomab for 1-4 weeks as induction therapy. Efficacy outcomes included complete remission (CR) and MRD negativity. Safety analysis included adverse events (AEs) including cytokine release syndrome (CRS) and neurological symptoms. Informed consent was obtained from all the patients. Results: Overall, 20 patients were enrolled. The median age of patients was 44 years (range, 8-92) and 12 (60%) patients had a risk factor. The median blast burden was 82.9% (range, 20.5-98). At the end of induction therapy, a complete remission rate of 100% was achieved after a median treatment duration of 25 days (range, 19-56); 17 (85%) patients achieved MRD negativity (<1 × 10-4). The median duration of blinatumomab infusion before achieving CR or MRD negativity was 14 days for both the outcomes (range, 7–28 for CR and 12–28 for MRD negativity). AEs were reported in 11 (55%) patients; 30% patients reported serious AEs (≥ grade 3) during induction therapy. Four patients had grade 3 AEs. No incidence of neurotoxicity or grade ≥3 CRS was reported. The median duration of neutrophil deficiency and platelet deficiency during the induction treatment was 10 days (range, 0–43) and 3 days (range, 0–51), respectively. At a median follow-up of 103 days (range, 31–334), overall survival was 100%. Summary/Conclusion: In this first real-world study in newly diagnosed Chinese B-ALL patients, blinatumomab demonstrated significant improvement in clinical outcomes irrespective of poor risk factors status and the pretreatment blast burden. This study successfully explored the dose balance between chemotherapy and blinatumomab, which could help improve survival outcomes and limit chemotherapy-related toxicity in B-ALL. Keywords: Real world data, Induction chemotherapy, B cell acute lymphoblastic leukemia